With the aging of population and the prolongation of life in recent years, medical care concerned with metabolic bone disease has attracted great attention from the aspects of QOL and increasing medical costs. The metabolic bone disease, referred to herein, includes not only so-called regressive bone diseases, but also bone disease due to aging, and metabolic bone diseases which are complications of renal failure and diabetes closely related to lifestyle in modern times. Since metabolic bone diseases range widely, how to proceed with handling the diseases poses a major social challenge. With this social background, scientific findings about metabolic bone diseases have been rapidly accumulated since the latter half of the 1980s.
Therapies of metabolic bone diseases are intensively implemented in combination with therapeutic techniques and development of drugs. As a result, the multiphasic properties (redundancies) of different drugs have been found. For example, hematopoietic factors and bone metabolism-related drugs have correlate mechanisms of action, or show similar actions, thus suggesting that they are closely correlated. Investigation and establishment of methods for treatment of metabolic bone diseases, using model animals suffering from metabolic bone diseases, make it possible to provide useful information leading to improvement of QOL in patients with metabolic bone diseases.
Bone diseases include those which involve a high risk for bone fracture, such as osteoporosis indicated by a decrease in bone mineral content. For such bone diseases, diagnostic instruments using the bone mineral content as a parameter (bone mineral analyzers), intended for the prevention and diagnosis of these diseases, have been markedly developed and technologically improved, because of their noninvasiveness and convenience.
In regard to diagnosis of metabolic bone disease, bone morphometric diagnosis based on morphological observation using bone labeling was developed in the 1970s. However, this diagnostic technique has difficulty in convenience, and is not so widely used as the bone mineral analyzer in the clinical setting.
An adenine-induced nephropathy model rat (adenine model) is a model animal with chronic renal failure 1), 2), 3). According to a report4), the bone density (bone mineral content) of the femur of the model was measured by a bone mineral analyzer, with attention being focused on the relationship between the renal failure in this model and a decrease in bone mineral content. A tendency toward decrease was observed in the bone mineral content, and the administration of EPO in this pathological state was found to produce a tendency toward recovery in the bone mineral content.
We, the inventors of the present invention, had closely investigated the adenine model from the aspects of renal failure and its complications. Based on the results of the investigation, we reported that the adenine model, in which renal failure developed, was a pathological model animal showing a complication, such as secondary hyperparathyroidism, ectopic calcification, or renal osteodystrophy which is a metabolic bone disease, the complication similar to a complication of renal failure in humans 5, 6).
To look into the essence of metabolic bone disease, such as renal osteodystrophy, it is an absolute necessity to make a final analysis by a histopathological method based on a quantitative balance between osteoblasts and osteoclasts in bone tissue, which are cells relevant to bone metabolism, and functional changes and changes with time in these cells, with the conception of time being taken into consideration. The noninvasive diagnostic method based on measurement of the bone mineral content, when used singly, was merely enough to indicate a suspicion of osteoporosis, etc. which are some of metabolic bone diseases. This diagnostic method did not enable analysis of the exact nature of the relevant metabolic bone disease and estimate its essence.